Peptide agonists of glp-1 activity

Abstract

Novel peptide agonists of GLP-1 activity useful for lowering blood glucose levels. The novel peptides comprise variants of the GLP-1 or the exendin-4 polypeptide sequence and are pharmacologically active and stable. These peptides are useful in the treatment of diseases that benefit from regulation of excess levels of blood glucose and/or regulation of gastric emptying, such as diabetes and eating disorders.

1 - 48 . (canceled) 
     
     
         49 . A method for producing a peptide conjugate having a polypeptide sequence of the formula: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 118) 
                 
                     
                   Lys 6 -Gly 8 -GLP-1 (7-36)-Lys 6 -NH 2   
                 
             
                
                
               
            
           
         
         the method comprising the steps of: 
         a) introducing a nucleic acid sequence encoding the polypeptide sequence and a selectable marker contained within a nucleic acid construct or a vector into a host cell to obtain a recombinant host cell; 
         b) selecting said recombinant host cell; 
         c) culturing said recombinant host cells under conditions permitting the production of said polypeptide sequence; 
         d) isolating said polypeptide sequence from the culture; and 
         e) optionally cleaving said polypeptide sequence using an appropriate protease to obtain said peptide conjugate. 
       
     
     
         50 . A method of reducing mortality and morbidity after myocardial infarction in a mammal comprising administering to the mammal a peptide of the formula:
 des Ala 35 -(Lys 40 (palmitoyl))exendin-4(1-39)-NH 2  (SEQ ID NO: 109),   the free acid thereof, or a pharmaceutically acceptable salt thereof, in an amount sufficient to reduce mortality and morbidity after myocardial infarction.   
     
     
         51 . A peptide of the formula:
 (Gly 8 ,Lys 37 (palmitoyl)-GLP-1(7-36)(Human)-Lys 7 -NH 2  (SEQ ID NO: 89),   the free acid thereof and a pharmaceutically acceptable salts thereof.   
     
     
         52 . A method of treating a condition associated with elevated blood glucose levels in a mammal comprising administering to the mammal a peptide of the formula: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 88) 
                 
                     
                   Gly 8 -GLP-1 (7-36)-Lys 6 -NH 2 , 
                 
             
                
                
               
            
           
         
         the free acid thereof, or a pharmaceutically acceptable salt thereof, in an amount sufficient to treat the condition. 
       
     
     
         53 . The method of  claim 52 , wherein the condition associated with elevated blood glucose levels is selected from type 1 diabetes, type 2 diabetes, insulin resistance syndrome, and hyperglycemia.